CD91 and its ligand gp96 confer cross-priming capabilities to multiple APCs during immune responses to nascent, emerging tumors

Cancer Immunol Res. 2024 Sep 13. doi: 10.1158/2326-6066.CIR-24-0326. Online ahead of print. ABSTRACT During cancer immunosurveillance, dendritic cells (DCs) play a central role in orchestrating T-cell responses against emerging tumors. Capture of miniscule amounts of antigen along with tumor-initiated costimulatory signals can drive maturation of DCs. Expression of CD91 on DCs is essential in cross-priming … Read more

Integrated germline and somatic features reveal divergent immune pathways driving response to immune checkpoint blockade

Cancer Immunol Res. 2024 Sep 10. doi: 10.1158/2326-6066.CIR-24-0164. Online ahead of print. ABSTRACT Immune Checkpoint Blockade (ICB) has revolutionized cancer treatment, however the mechanisms determining patient response remain poorly understood. Here, we used machine learning to predict ICB response from germline and somatic biomarkers and interpreted the learned model to uncover putative mechanisms driving superior … Read more

Spatially resolved whole-transcriptomic and proteomic profiling of lung cancer and its immune-microenvironment according to PD-L1 expression

Cancer Immunol Res. 2024 Sep 5. doi: 10.1158/2326-6066.CIR-24-0071. Online ahead of print. ABSTRACT The expression of PD-L1 on tumor cells (TCs) is used as an immunotherapy biomarker in lung cancer, but heterogeneous intratumoral expression is often observed. Using a Digital Spatial Profiling, we performed proteomic and whole-transcriptomic analyses of TCs and immune cells (ICs) in … Read more

Peripheral blood-derived PD-1/CD28-CD19-CAR-modified PD-1+ T-cell therapy in patients with solid tumors

T cells expressing PD-1 in the peripheral blood (PB) of patients with tumors possess therapeutic potential; however, the immunosuppressive, PD1-triggered signaling pathway and limited proliferative capacity of PD-1+ T cells present challenges to their therapeutic application. Here, we observed no discernible distinction between PD-1+ and PD-1- T cells in terms of clonal overlap. However, CD8+PD-1+ T cells from PB and tumor tissues exhibited tighter clustering based on clone size. Single-cell RNA…

CAR T cells engineered to secrete IFN-κ induce tumor ferroptosis via an IFNAR/STAT1/ACSL4 axis

Ferroptosis is an iron-dependent form of cell death that influences cancer immunity. Therapeutic modulation of ferroptosis is considered a potential strategy to enhance the efficacy of other cancer therapies, including immunotherapies such as chimeric antigen receptor (CAR) T cell therapy. In this study, we demonstrated that IFN-κ influenced the induction of ferroptosis. IFN-κ could enhance the sensitivity of tumor cells to ferroptosis induced by the small molecule compound erastin and the…

CD36+ pro-inflammatory macrophages interact with ZCCHC12+ tumor cells in papillary thyroid cancer promoting tumor progression and recurrence

Local recurrence and distal metastasis negatively impact the survival and quality of life in patients with papillary thyroid cancer (PTC). Therefore, identifying potential biomarkers and therapeutic targets for PTC is clinically crucial. In this study, we performed a multi-omics analysis that identified a subset of CD36+ pro-inflammatory macrophages within the tumor microenvironment of PTC. The recruitment of CD36+ macrophages to pre-malignant regions strongly correlated with unfavorable…

A single-cell analysis of the NK-cell landscape reveals that dietary restriction boosts NK cell antitumor immunity via Eomesdermin

Abnormal metabolism in tumor cells represents a potential target for tumor therapy. In this regard, dietary restriction (DR) or its combination with anticancer drugs is of interest as it can impede the growth of tumor cells. In addition to its effects on tumor cell, DR also plays an extrinsic role in restricting tumor growth by regulating immune cells. Natural killer (NK) cells are innate immune cells involved in tumor immunosurveillance. However, it remains uncertain whether DR can assist NK…

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